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Biology 12
Metabolism
In this unit we will be concentrating on protein enzymes that can be secreted from the cell or used within
the cell.
Enzymes are catalysts that cause chemical reactions to occur at lower activation energy – allow chemical
reactions to occur at lower temperatures, like 37 C in the human body.
Metabolism = refers to all of the chemical reactions within a cell or organism.
Metabolic Pathway
A series of enzyme “driven” chemical reactions that control the steps by which products of one reaction become
substrates for the next reaction.
A is the substrate for the 1st reaction and B is the product of the 1st reaction.
B becomes the substrate for the 2nd reaction and C is the product of the 2nd reaction.
C becomes the substrate for the 3rd reaction and D the end product of this metabolic pathway.
The numbers refer to specific enzymes for each reaction. Enzymes (called catalysts) help speed up a given reaction by
lowering the energy of activation for that reaction.
Energy of activation - the energy that must be supplied to cause molecules to react with one another is called the energy of
activation.
1.
2.
Some of the most important chemical reactions in the body are those called CELLULAR RESPIRATION that produce ATP.
The overall reaction for cellular respiration is: 38 ATP is the theoretical limit for ATP production from 1 glucose molecule.
C6H12O6 + 6O2
38 ATP + 6CO2 + 6H2O
Remember that ATP (Adenosine triphosphate) is a compound containing adenine and three phosphates, two of which are high energy
phosphates. ATP is the "common currency" of energy for most cellular processes.
A burst of energy will be released by removing the last phosphate group - this means that ATP can act as an energy store for the cell.
Countless ATP's move randomly around the cell so that they are available when needed.
ATP
ADP + P + energy
Cellular Respiration: The simplified metabolic pathway
C6H12O6
Mitochondrion
O2
B
D
C
No O2 available
4 ATP
E
H2O
F
38 ATP
Lactic acid
Lactate
H+
CO2
Fatty
acids
Carbohydrate
Amino
acids
NH3
Urea
Follow the Possible Reactions: (ALL of these reactions are catalyzed by enzymes)
1. Reactions from C6H12O6 – B – C – D – E – F
These reactions run if O2 is available in the cell (called aerobic cellular respiration). They produce a maximum of 38 ATP +
2 wastes products (H2O + CO2)
2. If O2 is not available then glucose will be metabolized to lactic acid. This reaction produces a maximum of 4 ATP and is
called anaerobic cellular respiration. The waste product lactic acid causes pH to drop in the surrounding tissue and blood.
The point at which lactic acid begins to accumulate in the blood is directly related to the lactate threshold because lactic
acid is converted to lactate. The drop in pH causes a drop in athletic performance as muscle proteins begin to denature (the
burn).
3. Fatty acids can be added as a substrate to produce ATP. The enzymes responsible for metabolizing fat can be increased
through exercise and diet BUT not by reducing calories. This is a complex topic and one that requires further research.
Becoming a fat ‘burner’ is very desirable because of the huge energy store in fat as well as other health benefits associated
with reducing body fat.
4. Under some circumstances, (over exercising or poor diet), amino acids can be added as a substrate to produce ATP. The
problem here is that these amino acids will be stripped away from muscle and immune system proteins to provide
‘emergency energy’. The amino acids are deaminated by removing the amine group. This leaves a carbohydrate like
substance that can be used as a substrate to produce ATP. The waste product NH3 (ammonia) is toxic and is converted to
urea in the liver. Both NH3 and urea need to excreted from the body in urine and sweat.
What are Enzymes?


Most enzymes are globular proteins – either tertiary or quaternary structure proteins.
Therefore, they are strings of amino acids that bend and fold into a particular 3d shape
A quaternary protein

When a protein folds it creates a shape that is called an active site.

Each enzyme is specific for one and ONLY one substrate (one lock - one key)




Substrates ‘fit’ into the active site.
Active site: part of the enzyme that fits with the substrate
Note that the active site has a specific fit for this particular substrate and no other.
This theory has some weaknesses, but it explains many basic things about enzyme function.
How Do Enzymes Work?
Enzyme, Substrate and Product
Enzyme:
a protein based catalyst that speeds up a specific reaction or type of reaction.
An enzyme is left unaltered by the reaction.
Substrate:
a reactant in a reaction controlled by an enzyme.
Product:
the end result of a chemical reaction.
Lock and Key Theory of Enzyme Action
Where:
E= Enzyme, S= Substrate, ES= Enzyme/substrate complex, P=Product.
Active site - This is where the substrates attach to the enzyme to become the enzyme- substrate complex.
Here they are changed (joined, split or molecularly rearranged) without the enzyme being changed itself.
Following disengagement, the new product is formed.
Protein portion of enzyme
The portion of an enzyme that deals with its specificity (the ability of the enzyme to speed up only one particular reaction).
Co-enzyme
The non-protein helper of an enzyme. A molecule that aids in the action of an enzyme, to which it is loosely bound.
They may be large molecules that the body is incapable of synthesizing. All well known vitamins are parts of co-enzymes.
Example of co-enzymes = B vitamins like Niacin (B3), Thiamine (B1) etc.
Protein enzyme
+
Coenzyme
Non –protein component
Active Enzyme
Types of Enzymes:
1. Hydrolytic Enzymes - used to digest (break apart) large molecules by hydrolysis.
All enzymes found in the digestive tract and in lysosomes are hydrolytic enzymes.
An Example of Lock and Key Theory
2. Dehydration Synthesis Enzymes - used to put molecules together by dehydration synthesis
An example of this process occurs in the liver and muscles where enzymes connect glucose unit molecules together
to produce glycogen.
An Example of Lock and Key Theory
Factors That Can Affect the Rate of an Enzyme Driven Reaction = yield factors
Certain factors influence the yield of enzymatic reactions
1. Genetic factors – inheritance, mutations and gene expression
2. Denaturation
3. Concentrations of enzymes and substrates
4. Competitive inhibition
1. Genetic factors – the ability to make protein enzymes is determined genetically.
a. Inheritance and mutation – enzyme production can be determined by the genes inherited from your parents.
The one gene – one enzyme theory suggests that each enzyme is produced by one gene. This hypothesis has been
proven for many enzymes but does not explain the production of all enzymes in the body. Some enzymes require
multiple genes for their production but we can understand the basics by understanding the one gene, one enzyme
theory.
Lactose intolerance - A simple example of gene inheritance and mutation.
Lactase is an enzyme that breaks down the disaccharide lactose (a sugar found in milk and other dairy products).
Lactase is produced by the lactase (LCT) gene.
Lactose
lactase
Where is the LCT gene located?
Glucose + Galactose
The LCT gene is located on the long (q) arm of chromosome 2 at position 21.
More precisely, the LCT gene is located from base pair 135,787,845 to base pair 135,837,180 on chromosome 2.
Since everyone has 2 of each chromosome, each person will have 2 copies of the LCT gene. There are 2 forms (alleles)
of the LCT gene – the wild type gene that produces active lactase enzyme (label as “A”) and the mutated gene that
produces mutated non-active lactase enzyme (label as “a”).
Label this allele as “A”
Label this allele as “a”
Possible genotype
(Type of genes inherited)
AA
homozygous wild type
Aa
heterozygous
aA
heterozygous
aa
homozygous mutated
Phenotype
(trait)
Can digest lactose
Can digest lactose but
may be reduced
Can digest lactose
but may be reduced
Lactose intolerant
Enzyme production
2 wild type genes means person has the ability to produce
sufficient lactase enzyme.
1 wild type gene and 1 mutated gene means person has ability to
produce some lactase enzyme.
1 wild type gene and 1 mutated gene means person has ability to
produce some lactase enzyme.
2 mutated genes means person does not have the ability to
produce lactase enzyme.
In the simplest sense, you can think of mutations as affecting the amount of particular proteins including enzymes.
b. Gene expression and epigenetics
To complicate the gene inheritance picture even further there are a number of factors that can affect gene expression.
These factors are called epigenetic factors.
Epigenetics means above the level of the genome (gene). For example, diet, exercise (activity), stress and other
environmental factors can influence how often a gene is read (transcribed and translated) and so affect the amount of
enzyme produced.
This genetic picture is even more complicated when you consider that the production of many enzymes require multiple
genes. Also, consider that metabolic pathways require many enzymes to catalyze the chemical reactions in the body.
At this stage in your biology career, it is important to recognize the concept of BIOCHEMICAL INDIVIDUALITY.
The uniqueness of each individual can be attributed to the combination of genetic and epigenetic factors that influence
the a person’s metabolism.
2.
Enzyme denaturation – the protein loses its normal shape and usually loses its function
Active (functional) protein
Denatured (non-functional protein
Denaturation of an enzyme = alters active site so that substrate can no longer fit.
Therefore, less ES complexes can be formed and fewer products produced
Enzyme Denaturation Factors
a. Heavy Metals - e.g. Lead and Mercury- These bond
with the protein in enzymes and thereby inactivate them.
b.
Temperature - Extremes, high temperatures will
change the shape of proteins and therefore, will damage
an enzyme. Within certain limits higher temps will
speed up enzyme action and cooler temperatures will
slow down the action. Every enzyme has its own
optimum range of action. Most human enzymes work
best around 37  C.
Initially, the increase in enzyme activity is due to
increasing molecular movement of both substrate
and enzyme.
c. pH - This affects ionic bonding between the side chains of molecules, particularly the "R" groups of the proteins.
This will change the shape of the mol. and therefore affect its performance. Each enzyme has its own optimum range
of pH to work efficiently.
environment
Pepsin works in the acidic
of the stomach.
Trypsin works in the slightly basic
environment of the small intestine
3. Concentrations
If the concentration of the substrate is increased, the amount of the product increases; that is, the more S or E
available, the more P there is within a certain amount of time. In many instances, the substrate is plentiful
within the cell, but the enzyme is present only in small amounts. The amount of enzyme limits the overall rate
of reaction.
In other words, if there is only a small amount of enzyme present, there will be fewer products in a given unit of time.
Enzymic reactions
Are faster but they reach a saturation point when all the enzyme
molecules are occupied.
If you increase the concentration of the enzyme then reaction rate
will increase too.
4. Competitive Inhibition
Reduction in rate of a reaction due to the presence of a compound that competes with the enzyme for the reactant (s)
so that less of the desired product is produced per unit time.
Competitive inhibitors block the active site so that few ES complexes can be formed
Hydrogen cyanide is an inhibitor for cytochrome oxidase (enzyme) - lethal effect on the human body.